The experiments described in this proposal are aimed at elucidation of the mechanisms by which the expression of both cellular and viral genes is regulated during the late phase of productive adenovirus infection of permissive human cells. Synthesis of mature, cellular mRNA species is blocked by the infection at some post-transcriptional step. We will therefore determine whether cellular mRNA sequences are processed normally, for example, whether they are capped and spliced, or whether the process by which mature mRNA molecules are normally transported from the nucleus is itself disrupted. Conditional lethal adenovirus mutants will be screened for failure to inhibit cellular mRNA, and therefore polypeptide, synthesis, to identify the viral function(s) responsible. The inhibition of synthesis of cellular ribosomal RNA species and of adenoviral early genes that occurs during the late phase of productive infection will also be analyzed to determine whether the expression of these two classes of genes is regulated by mechanisms analogous to that mediating inhibition of host mRNA synthesis. A study of the ribonucleoprotein structures containing adengviral RNA sequences present in infected cells during the late phase when only adenoviral RNA sequences are transported from the nucleus will also be initiated, in the hope of elucidating the role of such structures in the processing and/or transport of this discrete set of RNA sequences.